tbuckley/cabot-search huggingface dataset:
A Critical Need to Examine the Lack of Access to Healthy Quality Foods and Its Association With Cancer Mortality—A Clarion Call for Multilevel Research and Interventions
Authors: Karriem S. Watson, Angela Odoms-Young
Journal: JAMA Oncology (2023)

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Multicenter External Validation of the Deep Pelvic Endometriosis Index Magnetic Resonance Imaging Score
Authors: Isabelle Thomassin-Naggara, Michele Monroc, Benoit Chauveau, Arnaud Fauconnier, Pauline Verpillat, Yohann Dabi, Marie Gavrel, Pierre-Adrien Bolze, Emile Darai, Cyril Touboul, Samia Lamrabet, Pierre Collinet, Elise Zareski, Nicolas Bourdel, Horace Roman, Pascal Rousset
Journal: JAMA Network Open (2023)

Importance Preoperative mapping of deep pelvic endometriosis (DPE) is crucial as surgery can be complex and the quality of preoperative information is key. Objective To evaluate the Deep Pelvic Endometriosis Index (dPEI) magnetic resonance imaging (MRI) score in a multicenter cohort. Design, Setting, and Participants In this cohort study, the surgical databases of 7 French referral centers were retrospectively queried for women who underwent surgery and preoperative MRI for DPE between January 1, 2019, and December 31, 2020. Data were analyzed in October 2022. Intervention Magnetic resonance imaging scans were reviewed using a dedicated lexicon and classified according to the dPEI score. Main outcomes and measures Operating time, hospital stay, Clavien-Dindo–graded postoperative complications, and presence of de novo voiding dysfunction. Results The final cohort consisted of 605 women (mean age, 33.3; 95% CI, 32.7-33.8 years). A mild dPEI score was reported in 61.2% (370) of the women, moderate in 25.8% (156), and severe in 13.1% (79). Central endometriosis was described in 93.2% (564) of the women and lateral endometriosis in 31.2% (189). Lateral endometriosis was more frequent in severe (98.7%) vs moderate (48.7%) disease and in moderate vs mild (6.7%) disease according to the dPEI ( P &amp;amp;lt; .001). Median operating time (211 minutes) and hospital stay (6 days) were longer in severe DPE than in moderate DPE (operating time, 150 minutes; hospital stay 4 days; P &amp;amp;lt; .001), and in moderate than in mild DPE (operating time; 110 minutes; hospital stay, 3 days; P &amp;amp;lt; .001). Patients with severe disease were 3.6 times more likely to experience severe complications than patients with mild or moderate disease (odds ratio [OR], 3.6; 95% CI, 1.4-8.9; P = .004). They were also more likely to experience postoperative voiding dysfunction (OR, 3.5; 95% CI, 1.6-7.6; P = .001). Interobserver agreement between senior and junior readers was good (κ = 0.76; 95% CI, 0.65-0.86). Conclusions and Relevance The findings of this study suggest the ability of the dPEI to predict operating time, hospital stay, postoperative complications, and de novo postoperative voiding dysfunction in a multicenter cohort. The dPEI may help clinicians to better anticipate the extent of DPE and improve clinical management and patient counseling.
Silicate Nanoplatelets Promotes Neuronal Differentiation of Neural Stem Cells and Restoration of Spinal Cord Injury
Authors: Yifan Wang, Tengfei Zhao, Yiren Jiao, Hanxu Huang, Yongxiang Zhang, Ao Fang, Xuhua Wang, Yanling Zhou, Haochen Gu, Qionghua Wu, Jiang Chang, Fangcai Li, Kan Xu
Journal: Advanced Healthcare Materials (2023)

Neural stem cell (NSC) transplantation has been suggested as a promising therapeutic strategy to replace lost neurons after spinal cord injury (SCI). However, the low survival rate and neuronal differentiation efficiency of implanted NSCs within the lesion cavity limit the application. Furthermore, it is difficult for transplanted cells to form connections with host cells. Thus, effective and feasible methods to enhance the efficacy of cell transplantation are needed. In this study, the effect of Laponite nanoplatelets, a type of silicate nanoplatelets, on stem cell therapy is explored. Laponite nanoplatelets can induce the neuronal differentiation of NSCs in vitro within five days, and RNA sequencing and protein expression analysis demonstrated that the NF-κB pathway is involved in this process. Moreover, histological results revealed that Laponite nanoplatelets can increase the survival rate of transplanted NSCs and promote NSCs to differentiate into mature neurons. Finally, the formation of connections between transplanted cells and host cells is confirmed by axon tracing. Hence, Laponite nanoplatelets, which drove neuronal differentiation and the maturation of NSCs both in vitro and in vivo, can be considered a convenient and practical biomaterial to promote repair of the injured spinal cord by enhancing the efficacy of NSC transplantation.
Redefining Possible: Combining Phylogenomic and Supersparse Data in Frogs
Authors: Daniel M Portik, Jeffrey W Streicher, David C Blackburn, Daniel S Moen, Carl R Hutter, John J Wiens
Journal: Molecular Biology and Evolution (2023)

Abstract The data available for reconstructing molecular phylogenies have become wildly disparate. Phylogenomic studies can generate data for thousands of genetic markers for dozens of species, but for hundreds of other taxa, data may be available from only a few genes. Can these two types of data be integrated to combine the advantages of both, addressing the relationships of hundreds of species with thousands of genes? Here, we show that this is possible, using data from frogs. We generated a phylogenomic data set for 138 ingroup species and 3,784 nuclear markers (ultraconserved elements [UCEs]), including new UCE data from 70 species. We also assembled a supermatrix data set, including data from 97% of frog genera (441 total), with 1–307 genes per taxon. We then produced a combined phylogenomic–supermatrix data set (a “gigamatrix”) containing 441 ingroup taxa and 4,091 markers but with 86% missing data overall. Likelihood analysis of the gigamatrix yielded a generally well-supported tree among families, largely consistent with trees from the phylogenomic data alone. All terminal taxa were placed in the expected families, even though 42.5% of these taxa each had &amp;gt;99.5% missing data and 70.2% had &amp;gt;90% missing data. Our results show that missing data need not be an impediment to successfully combining very large phylogenomic and supermatrix data sets, and they open the door to new studies that simultaneously maximize sampling of genes and taxa.
Familial Clonal Hematopoiesis in a Long Telomere Syndrome
Authors: Emily A. DeBoy, Michael G. Tassia, Kristen E. Schratz, Stephanie M. Yan, Zoe L. Cosner, Emily J. McNally, Dustin L. Gable, Zhimin Xiang, David B. Lombard, Emmanuel S. Antonarakis, Christopher D. Gocke, Rajiv C. McCoy, Mary Armanios
Journal: New England Journal of Medicine (2023)

Telomere shortening is a well-characterized cellular aging mechanism, and short telomere syndromes cause age-related disease. However, whether long telomere length is advantageous is poorly understood.
In Vitro 3D Spheroid Model Preserves Tumor Microenvironment of Hot and Cold Breast Cancer Subtypes
Authors: Hemavathi Dhandapani, Armaan Siddiqui, Shivam Karadkar, Prakriti Tayalia
Journal: Advanced Healthcare Materials (2023)

Dynamic interaction of cancer, immune, and stromal cells with extracellular matrix components modulates and resists the response of standard care therapies. To mimic this, an in vitro 3D spheroid model is designed using liquid overlay method to simulate hot (MDA-MB-231) and cold (MCF-7) breast tumor microenvironment (TME). This study shows increased mesenchymal phenotype, stemness, and suppressive microenvironment in MDA-MB-231-spheroids upon exposure to doxorubicin. Intriguingly, the presence of human dermal fibroblasts enhances cancer-associated fibroblast phenotype in MDA-MB-231-spheroids through increased expression of CXCL12 and FSP-1, leading to higher infiltration of immune cells (THP-1 monocytes). However, a suppressive TME is observed in both subtypes, as seen by upregulation of M2-macrophage-specific CD68 and CD206 markers. Specifically, increased PDL-1 expressing tumor-associated macrophages along with FoxP3 expressing T regulatory cells are found in MDA-MB-231-spheroids when cultured with peripheral blood mononuclear cells. Further, it is found that the addition of 1-methyl-tryptophan, a potent indoleamine-2,3-dioxygenase-1 inhibitor, subsides the suppressive phenotype by decreasing the M2 polarization via downregulation of tryptophan metabolism and IL10 expression, particularly in MCF-7 triculture spheroids. Thus, the in vitro 3D spheroid model of TME can be utilized in therapeutics to validate immunomodulatory drugs for various breast cancer subtypes.
Entangling of Peptide Nanofibers Reduces the Invasiveness of SARS‐CoV‐2
Authors: Pei‐Pei Yang, Xin‐Wei Ye, Mei‐Qin Liu, Jin‐Xuan Yang, Xiao‐Li Feng, Yi‐Jing Li, Kuo Zhang, Hong‐Wen Liang, Yu Yi, Lei Wang, Yi‐Xuan Liu, Xing‐Lou Yang, Zheng‐Li Shi, Li‐Qiang Feng, Ling Chen, Yintong Xue, Qiang Pan‐Hammarström, Hao Wang, Yuliang Zhao
Journal: Advanced Healthcare Materials (2023)

The viral spike (S) protein on the surface of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) binds to angiotensin-converting enzyme 2 (ACE2) receptors on the host cells, facilitating its entry and infection. Here, functionalized nanofibers targeting the S protein with peptide sequences of IRQFFKK, WVHFYHK and NSGGSVH, which are screened from a high-throughput one-bead one-compound screening strategy, are designed and prepared. The flexible nanofibers support multiple binding sites and efficiently entangle SARS-CoV-2, forming a nanofibrous network that blocks the interaction between the S protein of SARS-CoV-2 and the ACE2 on host cells, and efficiently reduce the invasiveness of SARS-CoV-2. In summary, nanofibers entangling represents a smart nanomedicine for the prevention of SARS-CoV-2.
Is COVID-19 to Blame? Trends of Incidence and Sex Ratio in Youth-Onset Type 2 Diabetes in Germany
Authors: Christian Denzer, Joachim Rosenbauer, Daniela Klose, Antje Körner, Thomas Reinehr, Christina Baechle, Carmen Schröder, Susanna Wiegand, Reinhard W. Holl, Nicole Prinz
Journal: Diabetes Care (2023)

OBJECTIVE We investigated the incidence of pediatric type 2 diabetes (T2D) in Germany during 2 years of the coronavirus disease 2019 (COVID-19) pandemic (2020–2021) compared with the control period 2011–2019. RESEARCH DESIGN AND METHODS Data on T2D in children (aged 6 to &amp;lt;18 years) were obtained from the DPV (German Diabetes Prospective Follow-up) Registry. Poisson regression was used to estimate incidences for 2020 and 2021 based on data from 2011 to 2019, and these were compared with observed incidences in 2020 and 2021 by estimating incidence rate ratios (IRRs) with 95% CIs. RESULTS Incidence of youth-onset T2D increased from 0.75 per 100,000 patient-years (PYs) in 2011 (95% CI 0.58, 0.93) to 1.25 per 100,000 PYs in 2019 (95% CI 1.02, 1.48), an annual increase of 6.8% (95% CI 4.1, 9.6). In 2020, T2D incidence increased to 1.49 per 100,000 PYs (95% CI 1.23, 1.81), which was not significantly higher than predicted (IRR 1.15; 95% CI 0.90, 1.48). In 2021, the observed incidence was significantly higher than expected (1.95; 95% CI 1.65, 2.31 vs. 1.38; 95% CI 1.13, 1.69 per 100,000 PYs; IRR 1.41; 95% CI 1.12, 1.77). Although there was no significant increase in incidence in girls in 2021, the observed incidence in boys (2.16; 95% CI 1.73, 2.70 per 100,000 PYs) significantly exceeded the predicted rate (IRR 1.55; 95% CI 1.14, 2.12), leading to a reversal of the sex ratio of pediatric T2D incidence. CONCLUSIONS In Germany, incidence of pediatric T2D increased significantly in 2021. Adolescent boys were more affected by this increase, resulting in a reversal of the sex ratio of youth-onset T2D.
Bacterial Decolonization for Prevention of Radiation Dermatitis
Authors: Yana Kost, Alana Deutsch, Karolina Mieczkowska, Roya Nazarian, Ahava Muskat, H. Dean Hosgood, Juan Lin, Johanna P. Daily, Nitin Ohri, Rafi Kabarriti, Kosaku Shinoda, Beth N. McLellan
Journal: JAMA Oncology (2023)

Evidence-based approaches for the prevention of acute radiation dermatitis (ARD) are limited, and additional strategies are necessary to optimize care.
Weighing Antitumor Immunity against Life-threatening Myocarditis from Immune-Checkpoint Inhibitors
Authors: Michael Dougan
Journal: Cancer Discovery (2023)

Summary: In this issue of Cancer Discovery, Salem and colleagues report a combination therapy for immune-checkpoint inhibitor (ICI) myocarditis using high-dose glucocorticoids, abatacept, and the JAK inhibitor ruxolitinib. The apparent efficacy of their strategy and an accompanying animal model provide further evidence for common immune mechanisms underlying ICI toxicities. See related article by Salem et al., p. 1100 (2).
Diverse Antibacterial Treatments beyond Antibiotics for Diabetic Foot Ulcer Therapy
Authors: Xiaoyuan Li, Xin Jing, Ziqian Yu, Yubin Huang
Journal: Advanced Healthcare Materials (2023)

Abstract Diabetic foot ulcer (DFU), a common complication of diabetes, has become a great burden to both patients and the society. The delayed wound closure of ulcer sites resulting from vascular damage and neutrophil dysfunction facilitates bacterial infection. Once drug resistance occurs or bacterial biofilm is formed, conventional therapy tends to fail and amputation is unavoidable. Therefore, effective antibacterial treatment beyond antibiotics is of utmost importance to accelerate the wound healing process and prevent amputation. Considering the complexity of multidrug resistance, biofilm formation, and special microenvironments (such as hyperglycemia, hypoxia, and abnormal pH value) at the infected site of DFU, several antibacterial agents and different mechanisms have been explored to achieve the desired outcome. The present review focuses on the recent progress of antibacterial treatments, including metal‐based medications, natural and synthesized antimicrobial peptides, antibacterial polymers, and sensitizer‐based therapy. This review provides a valuable reference for the innovation of antibacterial material design for DFU therapy.
Provisional Mortality Data — United States, 2022
Authors: Farida B. Ahmad, Jodi A. Cisewski, Jiaquan Xu, Robert N. Anderson
Journal: MMWR Morbidity and Mortality Weekly Report (2023)

The National Center for Health Statistics' (NCHS) National Vital Statistics System (NVSS) collects and reports annual mortality statistics using U.S. death certificate data. Because of the time needed to investigate certain causes of death and to process and review death data, final annual mortality data for a given year are typically released 11 months after the end of the calendar year. Provisional data, which are based on the current flow of death certificate data to NCHS, provide an early estimate of deaths, before the release of final data. NVSS routinely releases provisional mortality data for all causes of death and for deaths associated with COVID-19.* This report is an overview of provisional U.S. mortality data for 2022, including a comparison with 2021 death rates. In 2022, approximately 3,273,705 deaths† occurred in the United States. The estimated 2022 age-adjusted death rate decreased by 5.3%, from 879.7 per 100,000 persons in 2021 to 832.8. COVID-19 was reported as the underlying cause or a contributing cause in an estimated 244,986 (7.5%) of those deaths (61.3 deaths per 100,000). The highest overall death rates by age, race and ethnicity, and sex occurred among persons who were aged ≥85 years, non-Hispanic American Indian or Alaska Native (AI/AN), non-Hispanic Black or African American (Black), and male. In 2022, the four leading causes of death were heart disease, cancer, unintentional injuries, and COVID-19. Provisional death estimates provide an early indication of shifts in mortality trends and can guide public health policies and interventions aimed at reducing mortality, including deaths directly or indirectly associated with the COVID-19 pandemic.
Common cardiovascular biomarkers can independently predict outcome of patients with Myelodysplastic syndromes
Authors: Ioannis Mitroulis, Vasileios Papadopoulos, Eleftheria Lamprianidou, Peter Mirtschink, Konstantinos Liapis, Kalliopi Zafeiropoulou, Alexandra Kourakli, Theodoros Moysiadis, Menelaos Papoutselis, George Vrachiolias, Argiris Symeonidis, Ioannis Kotsianidis
Journal: Blood Cancer Journal (2023)
Low Spontaneous Mutation Rate in Complex Multicellular Eukaryotes with a Haploid–Diploid Life Cycle
Authors: Marc Krasovec, Masakazu Hoshino, Min Zheng, Agnieszka P Lipinska, Susana M Coelho
Journal: Molecular Biology and Evolution (2023)

Abstract The spontaneous mutation rate µ is a crucial parameter to understand evolution and biodiversity. Mutation rates are highly variable across species, suggesting that µ is susceptible to selection and drift and that species life cycle and life history may impact its evolution. In particular, asexual reproduction and haploid selection are expected to affect the mutation rate, but very little empirical data are available to test this expectation. Here, we sequence 30 genomes of a parent–offspring pedigree in the model brown alga Ectocarpus sp.7, and 137 genomes of an interspecific cross of the closely related brown alga Scytosiphon to have access to the spontaneous mutation rate of representative organisms of a complex multicellular eukaryotic lineage outside animals and plants, and to evaluate the potential impact of life cycle on the mutation rate. Brown algae alternate between a haploid and a diploid stage, both multicellular and free living, and utilize both sexual and asexual reproduction. They are, therefore, excellent models to empirically test expectations of the effect of asexual reproduction and haploid selection on mutation rate evolution. We estimate that Ectocarpus has a base substitution rate of µbs = 4.07 × 10−10 per site per generation, whereas the Scytosiphon interspecific cross had µbs = 1.22 × 10−9. Overall, our estimations suggest that these brown algae, despite being multicellular complex eukaryotes, have unusually low mutation rates. In Ectocarpus, effective population size (Ne) could not entirely explain the low µbs. We propose that the haploid–diploid life cycle, combined with extensive asexual reproduction, may be additional key drivers of the mutation rate in these organisms.
Determinants of Covid19 disease and of survival after Covid19 in MPN patients treated with ruxolitinib
Authors: Francesca Palandri, Elena M. Elli, Giuseppe Auteri, Massimiliano Bonifacio, Giulia Benevolo, Florian H. Heidel, Simona Paglia, Malgorzata M. Trawinska, Costanza Bosi, Elena Rossi, Mario Tiribelli, Alessia Tieghi, Alessandra Iurlo, Nicola Polverelli, Giovanni Caocci, Gianni Binotto, Francesco Cavazzini, Eloise Beggiato, Daniela Cilloni, Caterina Tatarelli, Francesco Mendicino, Maurizio Miglino, Monica Bocchia, Monica Crugnola, Camilla Mazzoni, Andrea D. Romagnoli, Giovanni Rindone, Sara Ceglie, Alessandra D’Addio, Eleonora Santoni, Daniele Cattaneo, Daniela Bartoletti, Roberto M. Lemoli, Mauro Krampera, Antonio Cuneo, Gianpietro C. Semenzato, Roberto Latagliata, Elisabetta Abruzzese, Nicola Vianelli, Michele Cavo, Alessandro Andriani, Valerio De Stefano, Giuseppe A. Palumbo, Massimo Breccia
Journal: Blood Cancer Journal (2023)
Performance of Gut Microbiome as an Independent Diagnostic Tool for 20 Diseases: Cross-Cohort Validation of Machine-Learning Classifiers
Authors: Min Li, Jinxin Liu, Jiaying Zhu, Huarui Wang, Chuqing Sun, Na L. Gao, Xing-Ming Zhao, Wei-Hua Chen
Journal: Gut Microbes (2023)

Cross-cohort validation is essential for gut-microbiome-based disease stratification but was only performed for limited diseases. Here, we systematically evaluated the cross-cohort performance of gut microbiome-based machine-learning classifiers for 20 diseases. Using single-cohort classifiers, we obtained high predictive accuracies in intra-cohort validation (~0.77 AUC), but low accuracies in cross-cohort validation, except the intestinal diseases (~0.73 AUC). We then built combined-cohort classifiers trained on samples combined from multiple cohorts to improve the validation of non-intestinal diseases, and estimated the required sample size to achieve validation accuracies of >0.7. In addition, we observed higher validation performance for classifiers using metagenomic data than 16S amplicon data in intestinal diseases. We further quantified the cross-cohort marker consistency using a Marker Similarity Index and observed similar trends. Together, our results supported the gut microbiome as an independent diagnostic tool for intestinal diseases and revealed strategies to improve cross-cohort performance based on identified determinants of consistent cross-cohort gut microbiome alterations.
BCMA CAR-T induces complete and durable remission in refractory plasmablastic lymphoma
Authors: Sharmila Raghunandan, Melinda Pauly, William G Blum, Muna Qayed, Madhav V Dhodapkar, Mohamed Elkhalifa, Benjamin Watkins, Michelle Schoettler, Edwin Horwitz, Suhag Parikh, Shanmuganathan Chandrakasan, Kathryn Leung, Elyse Bryson, Laura Deeb, Jonathan L Kaufman, Diana Worthington-White, Adina Alazraki, Jordan M Schecter, Deepu Madduri, Carolyn C Jackson, Enrique Zudaire, Agne Taraseviciute-Morris, Alexander Babich, Tonia Nesheiwat, Martin Vogel, Nikoletta Lendvai, Lida Pacaud, Kirsten M Williams
Journal: Journal for ImmunoTherapy of Cancer (2023)

Plasmablastic lymphoma (PBL) is a rare subtype of aggressive large B-cell lymphoma, with a dismal prognosis despite aggressive therapies. New approaches are needed for those with refractory disease. PBL expresses antigens similar to multiple myeloma (MM), including B-cell maturation antigen (BCMA). Chimeric antigen receptor T-cell (CAR-T) therapy directed against BCMA has shown efficacy for the treatment of heavily pretreated MM with low rates of grades 3 and 4 cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) in a phase Ib/II trial (A Study of JNJ-68284528, a CAR-T Directed Against BCMA in Participants With Relapsed or Refractory Multiple Myeloma (CARTITUDE-1), NCT03548207 ). However, data for the use of BCMA CAR-T for treating PBL are lacking. We report a challenging case of multiple refractory PBL that emerged from B-cell acute lymphoblastic leukemia in an adolescent who failed to respond to an allogeneic hematopoietic cell transplant. The patient developed rapidly advancing disease despite withdrawal of immunosuppression, treatment with etoposide, ibrutinib, and daratumumab, prompting consideration of BCMA CAR-T (under emergency investigational new drug (eIND)). The patient achieved a complete remission (CR), without recurrent acute graft versus host disease (GVHD), CRS or ICANS after BCMA CAR-T therapy. BCMA CAR-T expansion was detected in vivo, peaking on day 15. The patient remains in CR for more than a year post CAR-T therapy, supporting consideration of immunotherapy for future patients with refractory PBL, a disease with few treatment options.